Seattle Genetics and its partner, Millennium: The Takeda Oncology Company, are following one of the well-traveled roads in cancer drug development. It’s about first gaining experience in the market by treating a small group of the very sickest patients, then working backwards until your drug eventually becomes part of the standard of care for more people who are newly diagnosed.
If the drug proves super-effective and safe over time, it could end up as part of “maintenance” therapy to keep the cancer from coming back.
It’s all part of the long-term strategy at Seattle Genetics (NASDAQ: SGEN), which will be on display next week at the American Society of Hematology‘s big annual meeting in San Diego. The company will have a handful of presentations this year about its antibody drug, brentuximab vedotin (Adcetris), for lymphomas. The treatment was initially cleared in the U.S. for patients with relapsed and treatment-resistant forms of Hodgkin’s lymphoma and anaplastic large cell lymphoma. But now Seattle Genetics and Millennium are preparing to release some results at ASH from a small trial of patients with a much healthier prognosis—those getting their first line of therapy for Hodgkin’s disease.
Genentech followed a similar strategy with its hit rituximab (Rituxan) for non-Hodgkin’s lymphoma, says Seattle Genetics CEO Clay Siegall. It started with relapsed, treatment-resistant patients, moved into the standard of care for newly diagnosed patients, and became part of maintenance therapy. If Seattle Genetics can duplicate the feat, it will significantly expand the potential market for its drug, and provide the first advance for this group of patients since the existing chemo regimen was established in 1977.
“After 34 years of there being no advances in front-line therapy, our goal is to increase the efficacy and decrease the toxicity,” Siegall says.
About 9,000 patients in the U.S., and a similar number in Europe, are diagnosed with Hodgkin’s each year, and are generally prescribed a cocktail of four chemotherapy drugs that essentially effective for 80-90 percent of patients, Siegall says. The bet for Seattle Genetics and Millennium is that the new antibody drug can raise the bar even higher on effectiveness, while reducing some of the nastier side effects of chemotherapy, including lung scarring.
The standard of care is a combination of chemotherapy drugs Adriamycin, bleomycin, vinblastine, and dacarbazine, known as ABVD. Based on feedback from top researchers, Seattle Genetics is testing the idea that the “B” in that regimen (bleomycin) might be the nastiest ingredient in the mix. The idea is to swap out bleomycin, and swap in the Seattle Genetics drug, Siegall says.
Researchers are keen to test this idea based on how the Seattle Genetics drug has performed in the sickest patients. The Seattle Genetics drug provided significant tumor shrinkage in 75 percent of patients with relapsed forms of Hodgkin’s disease in a clinical trial, and in about 86 percent of patients with anaplastic large-cell lymphoma. Researchers are still following patients to see how long those responses really do last, and to what extent they may help people live longer. The most common side effects found in clinical trials were a depletion in infection-fighting white blood cells, nerve damage in the fingers and toes, fatigue, nausea, and anemia. But most of the side effects were mild by cancer drug standards and the response rate was extraordinary given this group of patients had essentially run out of options, and entered the trial with a life expectancy of two to three years.
One of the key studies to watch on whether Seattle Genetics can take this drug to a larger group of Hodgkin’s patients will be presented Dec. 13 by Anas Younes of the University of Texas MD Anderson Cancer Center in Houston. That study was designed to enroll first-line Hodgkin’s patients on either the usual ABVD plus Adcetris in a variety of doses, or just AVD plus Adcetris.
Interim results, posted on the ASH website, show that six of 31 patients dropped out because of side effects, and that seven patients had to quit taking bleomycin because of side effects. Five of those seven patients were able to continue taking the Seattle Genetics drug along with AVD, researchers said. No patients died in the study, but researchers did say that 16 percent of patients had febrile neutropenia, which means patients had a significant depletion of their infection-fighting white-blood cells, combined with a fever.
Researchers labeled the side effects of the experimental regimen as “manageable” in the abstract. More updated data on safety, and the drug’s anti-tumor effect, will be made available at the meeting.
The data being presented next week at ASH is still interim, Siegall says, but there’s already enough information at this point for Seattle Genetics and Millennium to plan the next major step. That will be a global study of more than 880 patients getting first-line treatment for Hodgkin’s disease, Siegall says. The companies are still working on designing the study protocol, and signing up clinical trial sites around the world, but the goal is to start enrolling patients by the end of 2012 or early 2013, Siegall says. The upcoming study will be from the third of three phases of clinical trials normally required for FDA approval.
Siegall made it clear that moving Adcetris to first-line Hodgkin’s lymphoma is just the beginning of a broader program to bring the new drug to more patients.
“This is the pathway Rituxan went down,” Siegall says. “They started with relapsed, refractory patients. Then they went to front line patients, and then additional lymphomas.”